Strong Basic Conditions Research Articles

Phase-transfer-catalyzed enantioselective α-alkylation of aryl acetates

A chiral spirocyclic quaternary ammonium salt catalyzed asymmetric alkylation, especially methylation, of α-aryl esters possessing inherently poor reactivity under strong basic conditions has been developed, giving the target products with up to 94 % ee. This mild process was also applied to synthesize optically pure naproxen.

Stable Ozonides plus Vitamin E Acetate (Ozoile) for Treatment of Genitourinary Syndrome.

Background and Objectives: Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E is an important antioxidant diminishing the output of reactive oxygen species in the oxidation of fats and the emanation of free radicals, reducing cellular injury and aging. The primary aim of the present study was to assess the positive effects of an ozonide plus a vitamin E acetate-based compound (Ozoile) on genitourinary syndrome symptom relief after a maximum of 20 days of treatment. Materials and Methods: The inclusion criteria for patients' enrollment were women of child-bearing age or in menopause reporting genitourinary syndrome's related symptoms, such as pain, burning, a bad smell, dyspareunia, dryness, itching, bleeding, and nervousness. The exclusion criteria were Sjogren's syndrome and patients administered retinoic acid, an agent that causes mucosal dryness. Participants completed a questionnaire before and after 20 days of treatment. Results: The incidence of pain decreased from 16.7% to 11.8% (p-value < 0.0001). In addition, the mean symptom intensity decreased from 2.10 to 0.87 (p-value < 0.0001). Dryness was the most frequent pre-treatment symptom and decreased from 85.5% to 53.8% (p-value < 0.0001) (mean: 2.21 vs. 0.90; p-value < 0.0001). Conclusions: Ozoile was effective in reducing most gynecologic symptoms related to genitourinary syndrome. However, further studies are needed to compare its effect with other standards of care.

Hydrodynamics-engineered polyaniline nanofibers on graphene nanosheets for high-performance pH sensors

Real-time sweat monitoring in the human body using wearable sensors is promising for noninvasive and continuous healthcare applications. For reliable and accurate sweat analysis, further improvement in the response time and long-term stability of sensors is required. This paper reports an electrochemical pH sensor based on polyaniline/graphene (PANi-Gr) with rapid electron and ion transfer. The implementation of the Taylor–Couette flow approach allowed the efficient exfoliation of graphite into Gr nanosheets and the rapid polymerization of aniline monomers on the Gr surface, resulting in nanofiber PANi-deposited Gr nanocomposites. PANi-Gr had a large surface area and porous structure, which are favorable for rapid and stable electrochemical reactions. The screen-printed PANi-Gr-based pH sensor exhibited a Nernstian sensitivity of 61.91 mV/pH, rapid response time of <1 s, and long-term stability upon monitoring with minimal potential drift (0.04 mV h−1) under strong acidic and basic conditions. Furthermore, the on-body performance of the wearable pH sensor integrated with a wireless electronic device was analyzed via the noninvasive real-time monitoring of human sweat pH during stationary cycling. The developed sensor can be used in wearable real-time sweat monitoring devices for medical and healthcare applications.

Uracil-Cu(i) catalyst: allylation of cyclopropanols with Morita-Baylis-Hillman alcohols under water-tolerant conditions.

Inspired by the high affinity of copper with DNA and RNA, a uracil-copper catalytic system was developed to promote ring-opening allylation of cyclopropanols with allylic alcohols under water-tolerant conditions. A new C-OH bond-breaking model can well resolve the trade-off between the need for acidic activators for C(allyl)-OH bond cleavage and the demand for strong basic conditions for generating homoenolates. Therefore, Morita-Baylis-Hillman alcohols, rather than their pre-activated versions, could be incorporated directly into dehydrative cross-coupling with cyclopropanols delivering water as the only by-product. A variety of functionalized δ,ε-unsaturated ketones were obtained in good-to-high yield with high E-selectivity.

Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids with 1-Hydroxycyclohexyl Phenyl Ketone.

The oxidation of primary alcohols to the corresponding carboxylic acids is one of the fundamental and useful reactions in organic synthesis. In this paper, we report our comprehensive results toward the oxidation of primary alcohols and aldehydes to acids via hydride transfer reactions mediated by 1-hydroxycyclohexyl phenyl ketone. Under the strong basic conditions of sodium tert-butoxide, the room temperature oxidations tolerate a range of functional groups, including vulnerable tert-butanesulfinamides, amines, sulfides, olefins, and heterocycles, and provide good to excellent yields. Most importantly, our oxidation procedure can be applied to chemoselective oxidation of primary alcohols and aldehydes to carboxylic acids in the presence of secondary alcohols.

The influence of superbasic conditions and solvent effects on NMR spectra and structural parameters of acetylene in solution

Acetylene is a key industrial building block with a reach functionalization chemistry under strong basic (i.e., so called, superbasic) conditions in solution. In spite of significance of such acetylene transformations, mechanistic understanding of liquid-phase processes at molecular level under superbasic conditions remains a challenge. In the present study, a detailed comparative analysis of several factors influencing acetylene in solution was performed using NMR spectroscopy. Solvent effects, deuterium isotope effects, and temperature effects were estimated on experimental JCH spin–spin coupling constants and the chemical shift difference of ΔδC, and their possible outcome on acetylene bond length were assessed. Acetylene was studied under superbasic conditions in DMSO/KOH mixtures, and chemical exchange processes were observed, manifesting themselves as a coalescence of JCH. Possible exchange reactions are validated by quantum chemical calculations. The studied phenomenon may shed light on the mechanism of acetylene activation under superbasic conditions and contribute to understanding functionalization chemistry in the liquid phase.

Ammonium Acetate Catalyzed Formation of 1,5‐Benzodiazepines through [4+2+1] Cycloaddition Involving 5‐Hydroxymethylfurfural

AbstractThe use of the renewable platform molecule 5‐hydroxymethylfurfural (5‐HMF) in multi‐component reaction with a diamine and an alkynone to generate seven‐membered 1,5‐benzodiazepines is described. Due to the sensitivity of 5‐HMF to strong acidic and basic conditions, the investigation required an in‐depth revisit of reaction parameters as compared to benchmark aldehydes. Among catalysts/solvents couples, ammonium acetate in ethanol proved to be a clean and efficient system. These optimized conditions were subsequently used to investigate the scope of the reaction providing a library of 1,5‐benzodiazepines in moderate to good yields from a wide range of diversely substituted diamines and alkynones or alkyl alkynoates.

Two-Dimensional Benzobisthiazole-Vinylene-Linked Covalent Organic Frameworks Outperform One-Dimensional Counterparts in Photocatalysis

Vinylene/olefin-linked two-dimensional covalent organic frameworks (v-2D-COFs), featured with vinylene-linked in-plane conjugations, high chemical stabilities, and designable chemical structures, are promising for optoelectronic/photocatalytic applications. Developing v-2D-COFs with superior π-conjugation and optoelectronic properties is meaningful but remains challenging. In this work, we present the crystalline benzobisthiazole-bridged unsubstituted v-2D-COF (v-2D-COF-NS1 and v-2D-COF-NS2) synthesized via a benzothiazole-mediated aldol-type polycondensation. Interestingly, the resultant v-2D-COF exhibits a high chemical stability under both strong acidic (12 M HCl) and basic conditions (saturated KOH) due to the robust vinylene-linked skeletons. Moreover, the electron-deficient thiazole units and 2D π-conjugations endow v-2D-COFs (i.e., v-2D-COF-NS1) a narrow band gap of ∼1.85 eV with a conduction band of −3.65 eV vs vacuum, which are desirable for photocatalytic hydrogen evolution. As such, the v-2D-COF-NS1-based photoelectrode gives a photocurrent up to ∼47 μA cm–2 at 0.3 V vs reversible hydrogen electrode (RHE), which is much higher than the value of the corresponding linear polymer (LP-NS1) and outstanding among the reported COF photoelectrodes. Under a continuous visible light irradiation, v-2D-COF-NS1 generates hydrogen gas with an excellent rate of ∼4.4 mmol h–1 g–1 over 12 h. This work demonstrates the synthesis of unsubstituted v-2D-COFs that intrinsically contain benzobisthiazole-based building blocks and shows great potential in photocatalytic reactions.

Oxidation and degradation of (epi)gallocatechin gallate (EGCG/GCG) and (epi)catechin gallate (ECG/CG) in alkali solution

The oxidative decomposition/degradation of two main tea flavanols, EGCG/GCG and ECG/CG, was studied in alkaline solution under ultrasonic-assisted thermal conditions. The study employed HPLC–ESI-ToF-MS to identify the products generated by atmospheric oxygen oxidation and various base-catalyzed reactions. Strong basic condition led to accelerated hydrolysis and oxidation of EGCG/GCG and ECG/CG and yielded gallic acid, de-galloyl flavanols and corresponding o-quinone derivatives. Meanwhile, peroxidation or base-catalyzed cleavage and rearrangement occurred extensively on C- and B-rings of flavanol and generated various simpler aldehydes or acids. Besides, a number of dimers/trimers were produced. This contribution provides empirical proof of oxidative degradation of flavanols under strong alkaline condition. Meanwhile, detailed reaction mechanisms of C-/B-ring degradation and dimerization/polymerization phenomena are proposed to help understand the structural changes of flavanols under strong alkaline conditions.

Palladium-Catalyzed Aminocarbonylation of Isoquinolines Utilizing Chloroform-COware Chemistry.

The carbonyl group forms an integral part of several drug molecules and materials; hence, synthesis of carbonylated compounds remains an intriguing area of research for synthetic and medicinal chemists. Handling toxic CO gas has several limitations; thus, using safe and effective techniques for in or ex situ generation of carbon monoxide from nontoxic and cheap precursors is highly desirable. Among several precursors that have been explored for the generation of CO gas, chloroform can prove to be a promising CO surrogate due to its cost-effectiveness and ready availability. However, the one-pot chloroform-based carbonylation reaction requires strong basic conditions for hydrolysis of chloroform that may affect functional group tolerability of substrates and scale-up reactions. These limitations can be overcome by a two-chamber reactor (COware) that can be utilized for ex situ CO generation through hydrolysis of chloroform in one chamber and facilitating safe carbonylation reactions in another chamber under mild conditions. The versatility of this "Chloroform-COware" technique is explored through palladium-catalyzed aminocarbonylation of medicinally relevant heterocyclic cores, viz., isoquinoline and quinoline.

Coupling of sulfur and boron in carbonaceous material to strengthen persulfate activation for antibiotic degradation: Active sites, mechanism, and toxicity assessment

Carbon-mediated persulfate advanced oxidation processes (PS-AOPs) are appealing in contaminant remediation. For the first time, S,B-co-doped carbon-based persulfate activators were synthesized through direct carbonization of sodium lignosulfonate and boric acid. By degrading sulfamethoxazole (SMX), CSB-750 obtained 98.7% removal and 81.4% mineralization within 30 min. In comparison with solo S or B doping, S and B co-doped carbon showed the coupling effect for enhanced catalysis. The rate constant (kobs) of 0.1679 min–1 was 22.38- and 279.83-fold higher than those of CS-750 (0.0075 min–1) and CB-750 (0.0006 min–1), respectively. The degradation was efficient at strong acidic and weak basic conditions (pH 3–9). Substantial inhibition effect was presented at strong basic condition (pH 10.95) and in presence of CO32–. The CO32–-caused inhibition was the combined result of the cooperation of pH and quenching O2·–. Thiophene sulfur, BC3, BC2O, and structural defects were identified as the active sites for PS activation. Radical and nonradical pathways were both involved in the CSB-750/PS/SMX system, where 1O2 dominated the degradation, SO4·–, ·OH and direct electron transfer played the subordinate role, and O2·– served as a precursor for the formation of partial 1O2. The toxicity of degradation system, the effect of real water matrix, and the reusability of carbocatalysts were comprehensively analyzed. Nine possible degradation pathways were proposed. This work focuses on the catalytic performance improvement through the coupling effect of S,B co-doping, and develops an advanced heteroatom doping system to fabricate carbonaceous persulfate activators.

In-situ healing of damaged polyethersulfone ultrafiltration membranes with microgels

The damage of water treatment membranes under operation is a thorny problem, resulting in a great reduction of separation performance and compromised water quality. Here, we shall report a facile method for in-situ reparation of damaged membranes by using damaged polyethersulfone (PES) ultrafiltration (UF) flat membranes as model systems and quaternized crosslinked microgels coded as PNI6 microgels as the healing materials. The PNI6 microgels were synthesized via surfactant free emulsion polymerization of N-isopropylacrylamide (NIPAM) and 1-vinylimidazole (VIM) in the presence of 1,6-dibromohexane (BrCH). The obtained PNI6 microgel suspension was used as the feeding liquid to successfully heal the wound of damaged PES UF flat membranes by filtration deposition. An absorbed microgel layer was formed on the wound site of membranes and hence healed the wound. The rejection performances of microgel-healed PES UF membranes were recovered to the original level of pristine membranes although the water flux decreased from 588.6 L/(m2 h bar) for the pristine membrane to 228.8 L/(m2 h bar) for the healed membranes. It was also demonstrated that the microgel-healed PES UF membranes were chemically stable in both strong acidic and basic conditions and durable in a wide temperature range from 25 to 70 °C with a long-term stability.

Analysis of the isomerization of diketopiperazine consisting of proline and aromatic amino acid residues using nuclear magnetic resonance.

Under different concentrations of the base potassium deuteroxide KOD, the progress of reactions, such as enolization, D-substitution, isomerization, and conformational changes of diketopiperazine cyclo(L-Pro-L-Xxx) and cyclo(D-Pro-L-Xxx) (Xxx=Phe, Tyr) in D2O solution, was investigated by 1H nuclear magnetic resonance (NMR). Cyclo(L-Pro-L-Xxx) is mostly isomerized to cyclo(D-Pro-L-Xxx) in D2O solution, whereas cyclo(D-Pro-L-Xxx) is only slightly isomerized to cyclo(L-Pro-L-Xxx) even under stronger basic conditions. After adding a deuterated organic solvent (CD3COCD3, CD3SOCD3 or CD3OD) to a D2O solution of cyclo(L-Pro-L-Xxx), cyclo(D-Pro-L-Xxx), or increasing the temperature of the D2O solution, CH-π interaction between H9 and the benzene ring of cyclo (D-Pro-L-Xxx) was stronger than that between H8α and the benzene ring of cyclo(L-Pro-L-Xxx).

Sulfur-modified chitosan derived N,S-co-doped carbon as a bifunctional material for adsorption and catalytic degradation sulfamethoxazole by persulfate

N,S-co-doped carbons were synthesized through the calcination of sulfur-modified chitosan for the first time, and utilized as persulfate activators for sulfamethoxazole (SMX) remediation in water. The chitosan and sulfonyl chloride underwent one-step sulfonylation reaction to generate S-modified chitosan. The catalyst NSC-3 showed both excellent adsorption and catalytic oxidation efficiency, corresponding 98.62% removal and 81.34% mineralization rate within 90 min. The rate constant (kobs) was up to 0.0578 min−1, with 75.60-folders higher than that of sulfur-free catalyst NC (7.6580 ×10−4 min−1). The synergy of N and S contributed to the improvement of removal efficiency. The adsorption and oxidation performance were highly depended on the S/N atomic ratio. At the S/N ratio of 0.18, the maximum adsorption and oxidation capability were obtained. The NSC-3/PS system exhibited outstanding adaptability at the wide pH range from 3.07 to 9.28, while the inhibitory effect occurred at strong basic conditions (pH = 11.01). The thiophene sulfur and structural defects were identified as the catalytic sites in activating PS. Both radical and non-radical pathways were responsible for degradation process, where 1O2 played a major role, SO4·-exerted a minor contribution, and O2·- acts as the precursor for the production of 1O2. Another source of 1O2 was assigned to the activation of PS by structure defects. This work indicates that N,S-co-doped carbon at an optimal S/N atomic ratio effectively catalyzes persulfate, and provides an innovative method to construct bifunctional carbon materials of adsorption and oxidization.

Insights into Elution of Anion Exchange Cartridges: Opening the Path toward Aliphatic 18F-Radiolabeling of Base-Sensitive Tracers.

Aliphatic nucleophilic substitution (SN2) with [18F]fluoride is the most widely applied method to prepare 18F-labeled positron emission tomography (PET) tracers. Strong basic conditions commonly used during 18F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to trap [18F]fluoride on anion exchange cartridges and elute it afterward with basic anions. This sequence is used to facilitate the transfer of [18F]fluoride from an aqueous to an aprotic organic, polar reaction medium, which is beneficial for SN2 reactions. Furthermore, this sequence also removes cationic radioactive contaminations from cyclotron-irradiated [18O]water from which [18F]fluoride is produced. In this study, we developed an efficient elution procedure resulting in low basicity that permits SN2 18F-labeling of base-sensitive scaffolds. Extensive screening of trapping and elution conditions (>1000 experiments) and studying their influence on the radiochemical yield (RCY) allowed us to identify a suitable procedure for this. Using this procedure, four PET tracers and three synthons could be radiolabeled in substantially higher RCYs (up to 2.5-fold) compared to those of previously published procedures, even from lower precursor amounts. Encouraged by these results, we applied our low-basicity method to the radiolabeling of highly base-sensitive tetrazines, which cannot be labeled using state-of-art direct aliphatic 18F-labeling procedures. Labeling succeeded in RCYs of up to 20%. We believe that our findings facilitate PET tracer development by opening the path toward simple and direct SN2 18F fluorination of base-sensitive substrates.

Detoxification of Asbestos and Recovery of Valuable Metals from Detoxified Asbestos

Studies on detoxification of asbestos and recovery of valuable metals from detoxified asbestos were conducted. First, asbestos was detoxified by a microwave heat treatment that used silicon carbide balls, which are inorganic heating elements that absorb microwaves and release heat at room temperature. For efficient heat treatment, the asbestos containing waste (ACW) was powdered by crushing and grinding processes and then a detoxification heat treatment was performed. Microwave heat treatment temperature and time variables were adjusted to investigate the detoxification properties according to heat treatment conditions. After heat treatment, treated ACW was analyzed for detoxification properties through crystal structure and microstructure analysis using X‐ray diffraction (XRD) and scanning electron microscopy. Complete asbestos detoxification was confirmed when the microwave heat treatment was performed at 1200°C for over 60 min and at 1300°C for over 10 min. Second, recovery of valuable metals from detoxified asbestos was carried out. The main components, Si, Ca, and Mg, of detoxified asbestos‐containing waste (DACW) were separated and recovered in the form of SiO2, CaSO4, and Mg(OH)2. SiO2 was separated first after treatment of DACW with HCl. Ca in the form of sulfate, CaSO4, was recovered when subsequent treatment of remaining aqueous acid solution with H2SO4. The remaining Mg was recovered by precipitation as Mg(OH)2 form under strong basic conditions. Each separated component was confirmed by XRD and Inductively Coupled Plasma (ICP) analysis.

Expected and Unexpected Products in Half Curcuminoid Synthesis: Crystal Structures of But-3-en-2-ones and 3-Methylcyclohex-2-enones

The expected (E)-but-3-en-2-ones compounds I and II (half curcuminoids) were obtained by the Claisen–Schmidt reaction between aldehydes 3,4-dimethoxybenzaldehyde or 4-nitrobenzaldehyde with acetone. Concomitantly, 3-methylcyclohex-2-enones compounds III and IV arose from an unexpected reaction of but-3-en-2-ones in the cascade reaction of a Michael-type addition of a second molecule of acetone followed by Robinson annulation under strong basic conditions. Both enones exhibit the (E)-configuration, compound I displays s-trans conformation, whereas compound II exhibits conformational disorder as solid solution of s-cis and s-trans conformations. The related 3-methylcyclohex-2-enones exhibit envelope conformation. Compound III constitutes an example of the rarest case of racemic solid solution (pseudoracemate), where a lack of chiral discrimination with respect to the two enantiomers leads to an enantiomeric disorder of a racemic mixture with different occupancies at the reference site. Due to the lack of strong hydrogen-bond donors in all compounds, the crystal packing is mainly stabilized by weak intermolecular C-H···O interactions between the molecules. The present work provides a new perspective on the search for by-products normally overlooked in Claisen–Schmidt condensations.

A simple way to novel 2‐dichloromethyl‐5‐aryl‐2H‐tetrazoles

AbstractA series of 2‐dichloromethyl‐5‐aryl‐2H‐tetrazoles (3a–i) were synthesized by the reaction of 5‐aryl‐NH‐tetrazoles with trichloromethane in strong organic basic condition. The reaction represents a single‐stage access to a new class of promising compounds, which not only can have biological activity, but can also serve as intermediates for further alkylation of halogen and the introduction of various fragments into the structure. The compounds obtained were fully characterized by means of ESI–MS, 1H and 13C{1H} NMR spectroscopies, as well as by single‐crystal X‐ray diffraction (for 3b) the structural parameters as well as the vibrational corrections to enthalpies and total energies of the investigated systems were calculated using DFT B3LYP/6‐31+G** approach.

The unexpected reactivity of 9-iodo-nido-carborane: from nucleophilic substitution reactions to the synthesis of tricobalt tris(dicarbollide) Na[4,4',4''-(MeOCH2CH2O)3-3,3',3''-Co3(μ3-O)(μ3-S)(1,2-C2B9H10)3

An unusual reactivity of 9-iodo-nido-carborane [9-I-7,8-C2B9H11]- towards nucleophiles under strong basic conditions was revealed. The nucleophilic substitution of iodine with O- and N-nucleophiles results in [9-RO-7,8-C2B9H11]- (R = H, CH2CH2OMe) and [9-L-7,8-C2B9H11] (L = Py, NEt3, Me2NCH2CH2NMe2), respectively. Reaction of [9-I-7,8-C2B9H11]- with CoCl2 in 1,2-dimethoxyethane in the presence of t-BuOK, depending on the order of addition of the reagents, leads either to a diastereomeric mixture of diiodo derivatives cobalt bis(dicarbollide) rac-[4,4'-I2-3,3'-Co(1,2-C2B9H10)2]- and meso-[4,7'-I2-3,3'-Co(1,2-C2B9H10)2]- or to the corresponding mixture of 2-methoxyethoxy derivatives rac-[4,4'-(MeOCH2CH2O)2-3,3'-Co(1,2-C2B9H10)2]- and meso-[4,7'-(MeOCH2CH2O)2-3,3'-Co(1,2-C2B9H10)2]-. In the presence of accidental admixture of sodium thiosulfate, the reactions of 9-iodo-nido-carborane and 9-(2'-methoxyethoxy)-nido-carborane with CoCl2 in 1,2-dimethoxyethane were found to produce additionally unprecedented tricobalt tris(dicarbollide) cluster Na[4,4',4''-(MeOCH2CH2O)3-3,3',3''-Co3(μ3-O)(μ3-S)(1,2-C2B9H10)3], the central fragment of which is a trigonal bipyramid with apical oxygen and sulfur atoms, and the base is formed by the Co3 triangle flanked by three dicarbollide ligands. In addition, the 2-methoxyethoxy substituents of the dicarbollide ligands chelate the sodium cation in such a way that they form a helix whose rotation direction depends on the enantiomer of the parent ligand. Thus, in this case, induction of the helical chirality of the complex occurs due to the point chirality of the initial inorganic ligand. It is worth noting that in the case of symmetrically substituted 2-methoxyethoxy derivative of nido-carborane [10-MeOCH2CH2O-7,8-C2B9H11]- only formation of the corresponding cobalt bis(dicarbollide) complex [8,8'-(MeOCH2CH2O)2-3,3'-Co(1,2-C2B9H10)2]- was observed.

Thermo-Chemically Durable Perfluorinated Anion-Conducting Ionomer Membranes for Advanced Alkaline Water Electrolysis

The state-of-the-art membrane for alkaline water electrolysis is porous Zirfon®. Unfortunately, Zirfon® has been suffering from the crossover of hydrogen gas permeated through the pores, inducing safety issues including explosion. To date, there have been approaches to solve this problem. One good example is to use anion-conducting ionomer membranes with dense structures. Generally, the membranes, which are made up of hydrocarbon matrices, experience severe degradation, when they are exposed under strong basic conditions at the temperatures higher than 50 oC for high electrochemical performances. In this study, perfluorinated ionomer membranes with extremely high thermo-chemical resistances are developed via the combination of architectural design and supercritical dispersion.